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1.
J Neuroeng Rehabil ; 21(1): 123, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030574

ABSTRACT

BACKGROUND: Blood flow restriction (BFR) resistance training has demonstrated efficacy in promoting strength gains beneficial for rehabilitation. Yet, the distinct functional advantages of BFR strength training using high-load and low-load protocols remain unclear. This study explored the behavioral and neurophysiological mechanisms that explain the differing effects after volume-matched high-load and low-load BFR training. METHODS: Twenty-eight healthy participants were randomly assigned to the high-load blood flow restriction (BFR-HL, n = 14) and low-load blood flow restriction (BFR-LL, n = 14) groups. They underwent 3 weeks of BFR training for isometric wrist extension at intensities of 25% or 75% of maximal voluntary contraction (MVC) with matched training volume. Pre- and post-tests included MVC and trapezoidal force-tracking tests (0-75%-0% MVC) with multi-channel surface electromyography (EMG) from the extensor digitorum. RESULTS: The BFR-HL group exhibited a greater strength gain than that of the BFR-LL group after training (BFR_HL: 26.96 ± 16.33% vs. BFR_LL: 11.16 ± 15.34%)(p = 0.020). However, only the BFR-LL group showed improvement in force steadiness for tracking performance in the post-test (p = 0.004), indicated by a smaller normalized change in force fluctuations compared to the BFR-HL group (p = 0.048). After training, the BFR-HL group activated motor units (MUs) with higher recruitment thresholds (p < 0.001) and longer inter-spike intervals (p = 0.002), contrary to the BFR-LL group, who activated MUs with lower recruitment thresholds (p < 0.001) and shorter inter-spike intervals (p < 0.001) during force-tracking. The discharge variability (p < 0.003) and common drive index (p < 0.002) of MUs were consistently reduced with training for the two groups. CONCLUSIONS: BFR-HL training led to greater strength gains, while BFR-LL training better improved force precision control due to activation of MUs with lower recruitment thresholds and higher discharge rates.


Subject(s)
Electromyography , Resistance Training , Wrist , Humans , Male , Resistance Training/methods , Female , Wrist/physiology , Young Adult , Adult , Isometric Contraction/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/blood supply , Muscle Strength/physiology , Blood Flow Restriction Therapy/methods
2.
Bioengineering (Basel) ; 11(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39061757

ABSTRACT

In the field of dentistry, the presence of dental calculus is a commonly encountered issue. If not addressed promptly, it has the potential to lead to gum inflammation and eventual tooth loss. Bitewing (BW) images play a crucial role by providing a comprehensive visual representation of the tooth structure, allowing dentists to examine hard-to-reach areas with precision during clinical assessments. This visual aid significantly aids in the early detection of calculus, facilitating timely interventions and improving overall outcomes for patients. This study introduces a system designed for the detection of dental calculus in BW images, leveraging the power of YOLOv8 to identify individual teeth accurately. This system boasts an impressive precision rate of 97.48%, a recall (sensitivity) of 96.81%, and a specificity rate of 98.25%. Furthermore, this study introduces a novel approach to enhancing interdental edges through an advanced image-enhancement algorithm. This algorithm combines the use of a median filter and bilateral filter to refine the accuracy of convolutional neural networks in classifying dental calculus. Before image enhancement, the accuracy achieved using GoogLeNet stands at 75.00%, which significantly improves to 96.11% post-enhancement. These results hold the potential for streamlining dental consultations, enhancing the overall efficiency of dental services.

3.
Article in English | MEDLINE | ID: mdl-38780270

ABSTRACT

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1-2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats through optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) conditions. The results showed that contused animals had significantly lower spinal cord oxygenation levels than uninjured animals during normoxia. Peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure are significantly reduced following cervical spinal cord contusion. Notably, spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia elevated blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function in the acute phase after cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.


Subject(s)
Hyperoxia , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/metabolism , Male , Hyperoxia/physiopathology , Hyperoxia/blood , Rats , Oxygen/blood , Oxygen/metabolism , Spinal Cord/metabolism , Spinal Cord/blood supply , Spinal Cord/physiopathology , Cervical Cord/injuries , Cervical Cord/metabolism , Blood Pressure/physiology , Oxyhemoglobins/metabolism , Heart Rate/physiology
4.
Med Sci Sports Exerc ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38689440

ABSTRACT

PURPOSE: Despite its susceptibility to muscle fatigue, combined neuromuscular electrical stimulation (NMES) and blood flow restriction (BFR) is an effective regimen for managing muscle atrophy when traditional resistance exercises are not feasible. This study investigated the potential of low-level laser therapy (LLLT) in reducing muscle fatigue after the application of combined NMES and BFR. METHODS: Thirty-six healthy adults were divided into control and LLLT groups. The LLLT group received 60 J of 850 nm wavelength LLLT before a training program of combined NMES and BFR of the non-dominant extensor carpi radialis longus (ECRL). The control group followed the same protocol but received sham laser therapy. Assessments included maximal voluntary contraction (MVC), ECRL mechanical properties, and isometric force-tracking for wrist extension. RESULTS: The LLLT group exhibited a smaller normalized difference in MVC decrement (-4.01 ± 4.88%) than the control group (-23.85 ± 7.12%) (P < .001). The LLLT group demonstrated a smaller decrease in muscle stiffness of the ECRL compared to the control group, characterized by the smaller normalized changes in frequency (P = .002), stiffness (P = .002), and relaxation measures (P = .011) of mechanical oscillation waves. Unlike the control group, the LLLT group exhibited a smaller post-test increase in force fluctuations during force-tracking (P = .014), linked to the predominant recruitment of low-threshold MUs (P < .001) without fatigue-related increases in the discharge variability of high-threshold MUs (P > .05). CONCLUSIONS: LLLT pre-exposure reduces fatigue after combined NMES and BFR, preserving force generation, muscle stiffness, and force scaling. The functional benefits are achieved through fatigue-resistant activation strategies of motor unit recruitment and rate coding.

5.
Fish Shellfish Immunol ; 149: 109556, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608848

ABSTRACT

Japanese eel, Anguilla japonica, holds significant importance in Taiwanese aquaculture. With the intensification of eel farming, the impact of Edwardsiella tarda has become increasingly severe. Consequently, the abusive use of antibiotics has risen. Bacillus subtilis natto NTU-18, a strain of Bacillus with a high survival rate in feed processing, plays a crucial role in promoting intestinal health through competitive rejection, enhancing immune responses against bacterial pathogens, and improving intestinal health by modulating gastrointestinal microbiota to produce beneficial metabolites of mice and grass carp, Ctenopharyngodon idella. This study investigated the effects of different proportions (control, 0.25 %, 0.5 %, 1 %, and 2 %) of B. subtilis natto NTU-18 added to paste feed on the growth performance, intestinal morphology, and microbiota, expression of immune-related genes, and resistance to E. tarda in Japanese glass eel. The results indicated that the growth performance of all groups with B. subtilis natto NTU-18 added was significantly higher than that of the control group and did not impact the villi morphology. The expression of immune-related genes in the kidney, specifically HSP70 and SOD, was significantly higher from 0.5 % and above than the control; however, no significant differences were observed in CAT, POD, and HSP90. In the liver, significant differences were found in HSP70 and IgM above 0.25 % compared to the control group, with no significant differences in SOD, CAT, POD, and HSP90 among all groups. Additionally, intestinal microbiota analysis revealed that the 2 % additional group had significantly lower diversity than other groups, with Cetobacterium as the dominant species. The challenge test observed that the survival rates of the 0.5 % and 1 % groups were significantly higher. This research suggests that adding 0.5 % and 1 % of B. subtilis natto NTU-18 to the diet is beneficial for Japanese glass eel's immunity, growth performance, and disease resistance.


Subject(s)
Anguilla , Animal Feed , Bacillus subtilis , Diet , Disease Resistance , Fish Diseases , Gastrointestinal Microbiome , Intestines , Probiotics , Animals , Gastrointestinal Microbiome/drug effects , Anguilla/immunology , Anguilla/growth & development , Animal Feed/analysis , Disease Resistance/drug effects , Fish Diseases/immunology , Diet/veterinary , Probiotics/pharmacology , Probiotics/administration & dosage , Intestines/immunology , Enterobacteriaceae Infections/immunology , Enterobacteriaceae Infections/veterinary , Edwardsiella tarda/physiology , Dietary Supplements/analysis , Immunity, Innate , Random Allocation
6.
Sci Rep ; 14(1): 5310, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438474

ABSTRACT

Our study aimed to compare bone scintigraphy and dual-layer detector spectral CT (DLCT) with multiphase contrast enhancement for the diagnosis of osteoblastic bone lesions in patients with prostate cancer. The patients with prostate cancer and osteoblastic bone lesions detected on DLCT were divided into positive bone scintigraphy group (pBS) and negative bone scintigraphy group (nBS) based on bone scintigraphy. A total of 106 patients (57 nBS and 49 pBS) was included. The parameters of each lesion were measured from DLCT including Hounsfield unit (HU), 40-140 keV monochromatic HU, effective nuclear numbers (Zeff), and Iodine no water (InW) value in non-contrast phase (N), the arterial phase (A), and venous phase (V). The slope of the spectral curve at 40 and 100 keV, the different values of the parameters between A and N phase (A-N), V and N phase (V-N), and hybrid prediction model with multiparameters were used to differentiate pBS from nBS. Receiver operating characteristic analysis was performed to compare the area under the curve (AUC) for differentiating the pBS group from the nBS group. The value of conventional HU values, slope, and InW in A-N and V-N, and hybrid model were significantly higher in the pBS group than in the nBS group. The hybrid model of all significant parameters had the highest AUC of 0.988, with 95.5% sensitivity and 94.6% specificity. DLCT with arterial contrast enhancement phase has the potential to serve as an opportunistic screening tool for detecting positive osteoblastic bone lesions, corresponding to those identified in bone scintigraphy.


Subject(s)
Bone Diseases , Cartilage Diseases , Iodine , Prostatic Neoplasms , Male , Humans , Early Detection of Cancer , Tomography, X-Ray Computed , Mass Screening , Prostatic Neoplasms/diagnostic imaging , Radionuclide Imaging
7.
Small ; 20(24): e2311811, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38372500

ABSTRACT

Amid growing interest in using body heat for electricity in wearables, creating stretchable devices poses a major challenge. Herein, a hydrogel composed of two core constituents, namely the negatively-charged 2-acrylamido-2-methylpropanesulfonic acid and the zwitterionic (ZI) sulfobetaine acrylamide, is engineered into a double-network hydrogel. This results in a significant enhancement in mechanical properties, with tensile stress and strain of up to 470.3 kPa and 106.6%, respectively. Moreover, the ZI nature of the polymer enables the fabrication of a device with polar thermoelectric properties by modulating the pH. Thus, the ionic Seebeck coefficient (Si) of the ZI hydrogel ranges from -32.6 to 31.7 mV K-1 as the pH is varied from 1 to 14, giving substantial figure of merit (ZTi) values of 3.8 and 3.6, respectively. Moreover, a prototype stretchable ionic thermoelectric supercapacitor incorporating the ZI hydrogel exhibits notable power densities of 1.8 and 0.9 mW m-2 at pH 1 and 14, respectively. Thus, the present work paves the way for the utilization of pH-sensitive, stretchable ZI hydrogels for thermoelectric applications, with a specific focus on harvesting low-grade waste heat within the temperature range of 25-40 °C.

8.
J Proteome Res ; 23(3): 939-955, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38364797

ABSTRACT

N-Linked glycosylation is one of the most essential post-translational modifications of proteins. However, N-glycan structural determination remains challenging because of the small differences in structures between isomers. In this study, we constructed a database containing collision-induced dissociation MSn mass spectra and chromatograms of high-performance liquid chromatography for the rapid identification of high-mannose and paucimannose N-glycan isomers. These N-glycans include isomers by breaking of arbitrary numbers of glycosidic bonds at arbitrary positions of canonical Man9GlcNAc2 N-glycans. In addition, some GlcMannGlcNAc2 N-glycan isomers were included in the database. This database is particularly useful for the identification of the N-glycans not in conventional N-glycan standards. This study demonstrated the application of the database to structural assignment for high-mannose N-glycans extracted from bovine whey proteins, soybean proteins, human mammary epithelial cells, and human breast carcinoma cells. We found many N-glycans that are not expected to be generated by conventional biosynthetic pathways of multicellular eukaryotes.


Subject(s)
Breast , Mannose , Humans , Animals , Cattle , Chromatography, High Pressure Liquid , Databases, Factual , Polysaccharides
9.
Respir Res ; 25(1): 65, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38317222

ABSTRACT

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.


Subject(s)
Lung Diseases , Lung Neoplasms , Humans , Lung Diseases/diagnosis , Bronchoscopy , Image-Guided Biopsy , Lung Neoplasms/pathology , Biopsy , Cone-Beam Computed Tomography , Fluoroscopy , Retrospective Studies
10.
Bull Math Biol ; 86(3): 31, 2024 02 14.
Article in English | MEDLINE | ID: mdl-38353870

ABSTRACT

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data.


Subject(s)
COVID-19 , SARS-CoV-2 , United States/epidemiology , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Mathematical Concepts , Models, Biological , Vaccination
11.
Langmuir ; 40(3): 1658-1665, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38179938

ABSTRACT

The surface resistivity of boroaluminosilicate display glasses, which may affect the downstream display panel manufacturing, varies with the relative humidity (RH) of the environment, but the origin of this RH dependence has not been well understood. We have measured the water adsorption behavior on Corning Eagle XG (Glass-E) and Lotus NXT (Glass-L) glass panels using Brewster angle transmission infrared spectroscopy. The IR spectra of adsorbed water were analyzed to obtain the effective thickness of adsorbed water, the distribution of hydrogen-bonding interactions among the adsorbed water molecules, and the isosteric heat of water adsorption. These characteristics were compared with the electrical conductivity (inverse of resistivity) of these two glasses [Appl. Surf. Sci. 2015, 356, 1189]. This comparison revealed the correlation between the conductivity and the water layer structure, which could explain the surface resistivity difference between Glass-E and Glass-L as a function of RH. This study also disputed the previous hypothesis that the water adsorption isotherm would be governed by the areal density of the surface hydroxyl group; instead, it suggested that the network modifier ions may also play a critical role, especially in the intermediate RH regime.

12.
JCO Precis Oncol ; 8: e2300314, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38190582

ABSTRACT

PURPOSE: The Blood First Assay Screening Trial (BFAST) is a prospective study using next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) in treatment-naïve advanced/metastatic non-small-cell lung cancer (NSCLC). We compared liquid biopsy to tissue testing and analyzed genomic alterations in Taiwanese patients with NSCLC using the BFAST database. MATERIALS AND METHODS: A total of 269 patients underwent FoundationOne Liquid Companion Diagnostic (F1LCDx) assay at the National Taiwan University Hospital, of whom 264 underwent tissue-based genetic testing also. We analyzed the actionable mutations and the concordance between tissue-based genetic testing, which was limited to EGFR, ALK, ROS1, and BRAF, in a real-life clinical setting and blood-based NGS in the clinical trial. Additionally, we analyzed the co-occurring genomic alterations from the blood-based ctDNA assay. RESULTS: A total of 76.2% patients showed actionable mutations. Standard tissue testing did not detect known driver alterations in about 22.7% of the patients (sensitivity, 70.24%). Liquid NGS detected additional mutations (RET, KRAS, MET, and ErbB2) in 14% of the patients, which went undetected by the standard-of-care testing. The complementary use of ctDNA NGS increased the detection rate by 42%. The F1LCDx assay had a sensitivity of 83.41%. Lower tumor and metastasis stages predicted nondetected blood-based NGS ctDNA results. Common co-occurring mutations in the blood-based NGS ctDNA assay were TP53, DNMT3A, TET2, PIK3CA, CTNNB1, and RB1. Among the patients with EGFR-mutated NSCLC, TET2 co-occurring alterations correlated with shorter progression-free survival of EGFR tyrosine kinase inhibitor treatment. CONCLUSION: NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Circulating Tumor DNA/genetics , Prospective Studies , Protein-Tyrosine Kinases , Taiwan , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Proto-Oncogene Proteins , Genomics , ErbB Receptors/genetics
13.
medRxiv ; 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-34704095

ABSTRACT

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data. One-Sentence Summary: Using a compartmental model parameterized to reproduce available reports of new Coronavirus Disease 2019 (COVID-19) cases, we quantified the impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2) on regional epidemics in the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix.

14.
Oncology ; 102(4): 318-326, 2024.
Article in English | MEDLINE | ID: mdl-37778345

ABSTRACT

INTRODUCTION: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. METHODS: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. RESULTS: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35-1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12-0.85; p = 0.013). CONCLUSION: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs.


Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Non-Small-Cell Lung , Drug-Related Side Effects and Adverse Reactions , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/drug therapy , Antineoplastic Agents, Immunological/adverse effects , Retrospective Studies , Adrenal Cortex Hormones/adverse effects
15.
Cancer Med ; 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38140788

ABSTRACT

INTRODUCTION: According to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell-free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next-generation sequencing (NGS). METHODS: We prospectively enrolled patients with lung cancer with first-line EGFR-TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed. RESULTS: Totally, 86 patients were enrolled. Twenty-six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two-thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty-four of them were treated with osimertinib, and progression-free survival was longer in patients without detectable T790M in cfDNA than in patients with detectable T790M in cfDNA (p = 0.02). For the 31 T790M-negative patients, there were six with mesenchymal-epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6-RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively. CONCLUSIONS: NGS after EGFR-TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR-TKI resistance may find more patients with targetable cancers.

16.
ACS Appl Mater Interfaces ; 15(48): 56072-56083, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37982689

ABSTRACT

Mixed ionic-electronic conducting (MIEC) thermoelectric (TE) materials offer higher ionic conductivity and ionic Seebeck coefficient compared to those of purely ionic-conducting TE materials. These characteristics make them suitable for direct use in thermoelectric generators (TEGs) as the charge carriers can be effectively transported from one electrode to the other via the external circuit. In the present study, MIEC hydrogels are fabricated via the chemical cross-linking of polyacrylamide (PAAM) and polydopamine (PDA) to form a double network. In addition, electrically conducting carboxylated carbon nanotubes (CNT-COOH) are dispersed evenly within the hydrogel via sonication and interaction with the PDA. Moreover, the electrical properties of the hydrogel are further improved via the in situ polymerization of polyaniline (PANI). The presence of CNT-COOH facilitates the ionic conductivity and enhances the ionic Seebeck coefficient via ionic-electronic interactions between sodium ions and carboxyl groups on CNT-COOH, which can be observed in X-ray photoelectron spectroscopy results, thereby promoting the charge transport properties. As a result, the optimum device exhibits a remarkable ionic conductivity of 175.3 mS cm-1 and a high ionic Seebeck coefficient of 18.6 mV K-1, giving an ionic power factor (PFi) of 6.06 mW m-1 K-2 with a correspondingly impressive ionic figure of merit (ZTi) of 2.65. These values represent significant achievements within the field of gel-state organic TE materials. Finally, a wearable module is fabricated by embedding the PAAM/PDA/CNT-COOH/PANI hydrogel into a poly(dimethylsiloxane) mold. This configuration yields a high power density of 171.4 mW m-2, thus highlighting the considerable potential for manufacturing TEGs for wearable devices capable of harnessing waste heat.

17.
J Chem Theory Comput ; 19(20): 7187-7198, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37800673

ABSTRACT

It has become common to perform kinetic analysis using approximate Koopman operators that transform high-dimensional timeseries of observables into ranked dynamical modes. The key to the practical success of the approach is the identification of a set of observables that form a good basis on which to expand the slow relaxation modes. Good observables are, however, difficult to identify a priori and suboptimal choices can lead to significant underestimations of characteristic time scales. Leveraging the representation of slow dynamics in terms of Hidden Markov Models (HMM), we propose a simple and computationally efficient clustering procedure to infer surrogate observables that form a good basis for slow modes. We apply the approach to an analytically solvable model system as well as on three protein systems of different complexities. We consistently demonstrate that the inferred indicator functions can significantly improve the estimation of the leading eigenvalues of Koopman operators and correctly identify key states and transition time scales of stochastic systems, even when good observables are not known a priori.

18.
Biomacromolecules ; 24(11): 4759-4770, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37704189

ABSTRACT

Cellulose microfibrils (CMFs) are a major load-bearing component in plant cell walls. Thus, their structures have been studied extensively with spectroscopic and microscopic characterization methods, but the findings from these two approaches were inconsistent, which hampers the mechanistic understanding of cell wall mechanics. Here, we report the regiospecific assembly of CMFs in the periclinal wall of plant epidermal cells. Using sum frequency generation spectroscopic imaging, we found that CMFs are highly aligned in the cell edge region where two cells form a junction, whereas they are mostly isotropic on average throughout the wall thickness in the flat face region of the epidermal cell. This subcellular-level heterogeneity in the CMF alignment provided a new perspective on tissue-level anisotropy in the tensile modulus of cell wall materials. This finding also has resolved a previous contradiction between the spectroscopic and microscopic imaging studies, which paves a foundation for better understanding of the cell wall architecture, especially structure-geometry relationships.


Subject(s)
Cellulose , Plant Cells , Cellulose/chemistry , Anisotropy , Microfibrils/chemistry , Cell Wall/chemistry
19.
J Biomed Sci ; 30(1): 80, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37726723

ABSTRACT

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.


Subject(s)
Lung Neoplasms , RNA, Long Noncoding , Animals , Mice , RNA, Long Noncoding/genetics , In Situ Hybridization, Fluorescence , Lung Neoplasms/genetics , Signal Transduction/genetics , Lung
20.
Epidemics ; 45: 100718, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37757572

ABSTRACT

The initial contagiousness of a communicable disease within a given population is quantified by the basic reproduction number, R0. This number depends on both pathogen and population properties. On the basis of compartmental models that reproduce Coronavirus Disease 2019 (COVID-19) surveillance data, we used Bayesian inference and the next-generation matrix approach to estimate region-specific R0 values for 280 of 384 metropolitan statistical areas (MSAs) in the United States (US), which account for 95% of the US population living in urban areas and 82% of the total population. We focused on MSA populations after finding that these populations were more uniformly impacted by COVID-19 than state populations. Our maximum a posteriori (MAP) estimates for R0 range from 1.9 to 7.7 and quantify the relative susceptibilities of regional populations to spread of respiratory diseases. ONE-SENTENCE SUMMARY: Initial contagiousness of Coronavirus Disease 2019 varied over a 4-fold range across urban areas of the United States.


Subject(s)
COVID-19 , Humans , United States/epidemiology , Bayes Theorem , COVID-19/epidemiology , Basic Reproduction Number
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